title: Partial PLP1 deletion causing X-linked dominant spastic paraplegia type 2.
abstract: BACKGROUND
  Proteolipid protein 1 gene (PLP1) mutations result in a continuum of neurological findings characterized by X-linked hypomyelinating leukodystrophies of the central nervous system, from mild spastic paraplegia type 2 to severe Pelizaeus-Merzbacher disease.
  
  
  METHODS
  We report spastic paraplegia type 2 in three individuals in one family. A 29-year-old man developed progressive spastic quadriplegia from early childhood with dysarthria, ataxia, dysphagia, and intellectual delay, but he displayed no nystagmus. His mother developed adult-onset mild spastic diplegia with dementia developing in later life, whereas his sister exhibited spastic diplegia from childhood, complicated by motor developmental delay and dysphagia. All three individuals had initially mild but progressive neurological phenotypes, no nystagmus, normal brainstem auditory-evoked potentials, and demyelinating peripheral neuropathy, but with varying clinical severity.
  
  
  RESULTS
  A 33-kb deletion encompassing exon 2 to 7 of PLP1 was identified in all three patients. Cloning of the junction fragment of the genomic recombination revealed a short palindromic sequence at the distal breakpoint, potentially facilitating a double-strand deoxyribonucleic acid break, followed by nonhomologous end joining. X-inactivation study and sequencing of the undeleted PLP1 alleles failed to explain the differences in severity between the two female patients.
  
  
  CONCLUSIONS
  PLP1 partial deletion is a rare cause of spastic paraplegia type 2 and exhibits X-linked dominant inheritance with variable expressivity.
authors.affiliation: Yanagawa Institute for Developmental Disabilities, Fukuoka, Japan. Electronic address: eea000346492@izm.bbiq.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Matsufuji
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.forename: Leo
authors.initials: L
authors.lastname: Gotoh
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimbo
authors.forename: Sachio
authors.initials: S
authors.lastname: Takashima
authors.forename: Ken
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018991:Myelin Proteolipid Protein / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology
chemical_list: D018991:Myelin Proteolipid Protein; C472930:PLP1 protein, human
keywords: Pelizaeus-Merzbacher disease; deletion; hypomyelinating leukodystrophy; myelin; non-homologous end joining; palindrome; proteolipid protein 1; spastic paraplegia type 2